These experiments are designed to determine whether there is some alteration in beta-adrenergic receptor function in patients with affective disorders. This will be evaluated by measuring both adenylate cyclase activity and the specific binding of (minus) 3H-alprenolol in leukocytes and erythrocytes obtained from patients with affective disorders. The binding of (minus) 3H-alprenolol provides a measure of the relative number of beta-adrenergic receptor sites. Both cross-sectional and longitudinal studies will be performed with these studies being done in patients prior to treatment and during different phases of the patient's illness. In addition, we will explore the effects of antidepressant drugs on adrenergic receptor sensitivity by measuring norepinephrine-induced stimulation of 3H-cyclic AMP net synthesis in limbic forebrain slices of the rat. These experiments are directed toward the possibility that late-developing effects of antidepressant drugs on this system may have a more significant relationship to their clinical activity than some of their acute effects. This idea will be tested indirectly by determining whether agents like triiodothyronine or tryptophan, which increase the speed of onset of action of antidepressant drugs, also increase the speed of development of drug-induced changes in 3H-cyclic AMP net synthesis. BIBLIOGRAPHIC REFERENCES: Frazer, A. and Mendels, J.: Use of L-DOPA in depression. Advances in Biochemical Psychopharmacology 16:671-675, 1977. Frazer, A. and Mendels, J.: Do tricyclic antidepressants enhace adrenergic transmission? American Journal of Psychiatry, 1977, in press.